After only five League appearances, he signed for Shamrock Rovers in September 1983.

After having won his third League of Ireland title with Shamrock Rovers in 1986, and making six appearances in European competition and 118 total appearances, O'Brien became Ron Atkinson's last signing as manager of Manchester United. He joined the Reds for an initial fee of £50,000.[3]

Alex Ferguson took over from Atkinson as manager in November 1986, and O'Brien made his debut in the 1986–87 season, making nine appearances, including an appearance in January 1987 where he was shown a red card just 85 seconds into a game against Southampton. The sending-off is the quickest dismissal in club history.[4] The majority of his appearances in the 1987–88 season were as a substitute, and that summer, frustrated by lack of first-team opportunities, he joined Newcastle United in a £275,000 move after 36 appearances (31 in the League) & two goals for Manchester United.

His career at St James' Park brought mixed fortunes. O'Brien suffered relegation from the top flight in the 1988–89 season. However, he played a major role as Newcastle won the First Division title in 1993, making 33 appearances and scoring six goals.

O'Brien found himself surplus to requirements as Newcastle rejoined the top flight and subsequently made a £350,000 move to Tranmere Rovers after a successful loan period. After Tranmere, he signed for Cork City, where he played in the UEFA Cup before returning to Bohemians in 2000 as player-coach. He enjoyed some great European nights during this season as Bohs knocked out Aberdeen and beat 1.FC Kaiserslautern. He also played a part as Bohs won the League and Cup Double before retiring as a player.

After retiring as a player, O'Brien had spells as assistant manager at Bohemians and Shamrock Rovers. He was appointed first team coach of Hibernian in November 2011 by Pat Fenlon.[5] O'Brien left Hibernian after the end of the 2012–13 season.